Effect of Motor State on Postactivation Depression of the Soleus H-Reflex in Parkinson's Disease During Deep Brain Stimulation and Dopaminergic Medication Treatment: A Pilot Study.

PURPOSE: Postactivation depression of the Hoffmann reflex is reduced in Parkinson's disease (PD), but how the recovery is influenced by the state of the muscle is unknown. The present pilot study examined postactivation depression in PD at rest and during a voluntary contraction while patients were off treatment and while receiving medications and/or deep brain stimulation. METHODS: The authors recruited nine patients with PD treated with implanted deep brain stimulation and examined postactivation depression under four treatment conditions. Paired pulses were delivered 25 to 300 ms apart, and soleus Hoffmann reflex recovery was tested at rest and during voluntary plantar flexion. Trials were matched for background muscle activity and compared with 10 age-matched controls. RESULTS: Patients with Parkinson disease who were OFF medications (OFF meds) and OFF stimulation (OFF stim) at rest showed less postactivation depression at the 300 ms interpulse interval (86.1% ± 21.0%) relative to control subjects (36.4% ± 6.1%; P < 0.05). Postactivation depression was restored when dopaminergic medication and/or deep brain stimulation was applied. Comparisons between resting and active motor states revealed that the recovery curves were similar OFF meds/OFF stim owing to faster recovery in PD seen at rest. In contrast, the effect of the motor state was different ON meds/OFF stim and ON meds/ON stim (both P < 0.05), with a nonsignificant trend OFF meds/ON stim ( P > 0.08). During a contraction, recovery curves were similar between all treatment conditions in PD and control. CONCLUSIONS: Disrupted Hoffmann reflex recovery is restored to control levels in PD patients at rest when receiving medications and/or deep brain stimulation or when engaged in voluntary contraction.

Effects of Deep Brain Stimulation and Dopaminergic Medication on Excitatory and Inhibitory Spinal Pathways in Parkinson Disease.

PURPOSE: Abnormal activity within the corticospinal system is believed to contribute to the motor dysfunction associated with Parkinson disease. However, the effect of treatment for parkinsonian motor symptoms on dysfunctional descending input to the motor neuron pool remains unclear. METHODS: We recruited nine patients with PD treated with deep brain stimulation and examined the time course of interaction between a conditioning pulse from transcranial magnetic stimulation and the soleus H-reflex. Patients with Parkinson disease were examined under four treatment conditions and compared with 10 age-matched control subjects. RESULTS: In healthy controls, transcranial magnetic stimulation conditioning led to early inhibition of the H-reflex (76.2% ± 6.3%) at a condition-test interval of -2 ms. This early inhibition was absent when patients were OFF medication/OFF stimulation (132.5% ± 20.4%; P > 0.05) but was maximally restored toward control levels ON medication/ON stimulation (80.3% ± 7.0%). Of note, early inhibition ON medication/ON stimulation tended to be stronger than when medication (85.4% ± 5.9%) or deep brain stimulation (95.7% ± 9.4%) were applied separately. Late facilitation was observed in controls at condition-test intervals ≥5 ms but was significantly reduced (by 50% to 80% of controls) in Parkinson disease OFF stimulation at condition-test intervals ≥15 ms. The late facilitation was akin to control subjects when patients were ON stimulation. CONCLUSIONS: The present pilot study demonstrates that the recruitment of early inhibition and late facilitation is disrupted in untreated Parkinson disease and that medication and deep brain stimulation may act together to normalize supraspinal drive to the motor neuron pool.

Intraoperative changes in the H-reflex pathway during deep brain stimulation surgery for Parkinson's disease: A potential biomarker for optimal electrode placement.

BACKGROUND: Deep Brain Stimulation (DBS) targeting the subthalamic nucleus (STN) and globus pallidus interna (GPi) is an effective treatment for cardinal motor symptoms and motor complications in Parkinson's Disease (PD). However, malpositioned DBS electrodes can result in suboptimal therapeutic response. OBJECTIVE: We explored whether recovery of the H-reflex-an easily measured electrophysiological analogue of the stretch reflex, known to be altered in PD-could serve as an adjunct biomarker of suboptimal versus optimal electrode position during STN- or GPi-DBS implantation. METHODS: Changes in soleus H-reflex recovery were investigated intraoperatively throughout awake DBS target refinement across 26 nuclei (14 STN). H-reflex recovery was evaluated during microelectrode recording (MER) and macrostimulation at multiple locations within and outside target nuclei, at varying stimulus intensities. RESULTS: Following MER, H-reflex recovery normalized (i.e., became less Parkinsonian) in 21/26 nuclei, and correlated with on-table motor improvement consistent with an insertional effect. During macrostimulation, H-reflex recovery was maximally normalized in 23/26 nuclei when current was applied at the location within the nucleus producing optimal motor benefit. At these optimal sites, H-reflex normalization was greatest at stimulation intensities generating maximum motor benefit free of stimulation-induced side effects, with subthreshold or suprathreshold intensities generating less dramatic normalization. CONCLUSION: H-reflex recovery is modulated by stimulation of the STN or GPi in patients with PD and varies depending on the location and intensity of stimulation within the target nucleus. H-reflex recovery shows potential as an easily-measured, objective, patient-specific, adjunct biomarker of suboptimal versus optimal electrode position during DBS surgery for PD.

Characterizing the effect of low intensity transcranial magnetic stimulation on the soleus H-reflex at rest.

Modulation of a Hoffmann (H)-reflex following transcranial magnetic stimulation (TMS) has been used to assess the nature of signals transmitted from cortical centers to lower motor neurons. Further characterizing the recruitment and time-course of the TMS-induced effect onto the soleus H-reflex adds to the discussion of these pathways and may improve its utility in clinical studies. In 10 healthy controls, TMS was used to condition the soleus H-reflex using TMS intensities from 65 to 110% of the resting motor threshold (RMT). Early facilitation [- 5 to - 3 ms condition-test (C-T) interval] was evident when TMS was 110% of RMT (P < 0.05). By comparison, late facilitation (+ 10 to + 20 ms C-T interval) was several times larger and observed over a wider range of TMS intensities, including 65-110% of RMT. The early inhibition (- 3 to - 1 ms C-T interval) had a low TMS threshold and was elicited over a wide range of intensity from 65% to 95% of RMT (all P < 0.05). A second inhibitory phase was seen ~ 4 ms later (+ 1 to + 4 ms C-T intervals) and was only observed for a TMS intensity of 95% of RMT (P < 0.05). The present findings reaffirm that subthreshold TMS strongly modulates soleus motor neurons and demonstrates that distinct pathways can be selectively probed at discrete C-T intervals when using specific TMS intensities.

Training-Specific Neural Plasticity in Spinal Reflexes after Incomplete Spinal Cord Injury.

The neural plasticity of spinal reflexes after two contrasting forms of walking training was determined in individuals with chronic, motor-incomplete spinal cord injury (SCI). Endurance Training involved treadmill walking for as long as possible, and Precision Training involved walking precisely over obstacles and onto targets overground. Twenty participants started either Endurance or Precision Training for 2 months and then crossed over after a 2-month rest period to the other form of training for 2 months. Measures were taken before and after each phase of training and rest. The cutaneomuscular reflex (CMR) during walking was evoked in the soleus (SOL) and tibialis anterior muscles by stimulating the posterior tibial nerve at the ankle. Clonus was estimated from the EMG power in the SOL during unperturbed walking. The inhibitory component of the SOL CMR was enhanced after Endurance but not Precision Training. Clonus did not change after either form of training. Participants with lower reflex excitability tended to be better walkers (i.e., faster walking speeds) prior to training, and the reduction in clonus was significantly correlated with the improvement in walking speed and distance. Thus, reflex excitability responded in a training-specific way, with the reduction in reflex excitability related to improvements in walking function. Trial registration number is NCT01765153.

Intraoperative spinal cord monitoring using low intensity transcranial stimulation to remove post-activation depression of the H-reflex.

OBJECTIVE: To investigate whether low intensity transcranial electrical stimulation (TES) can be used to condition post-activation depression of the H-reflex and simultaneously monitor the integrity of spinal motor pathways during spinal deformity correction surgery. METHODS: In 20 pediatric patients undergoing corrective surgery for spinal deformity, post-activation depression of the medial gastrocnemius H-reflex was initiated by delivering two pulses 50-125ms apart, and the second H-reflex was conditioned by TES. RESULTS: Low intensity TES caused no visible shoulder or trunk movements during 19/20 procedures and the stimulation reduced post-activation depression of the H-reflex. The interaction was present in 20/20 patients and did not diminish throughout the surgical period. In one case, the conditioning effect was lost within minutes of the disappearance of the lower extremity motor evoked potentials. CONCLUSION: Post-activation depression was used to detect the arrival of a subthreshold motor evoked potential at the lower motor neuron. The interaction produced minimal movement within the surgical field and remained stable throughout the surgical period. SIGNIFICANCE: This is the first use of post-activation depression during intraoperative neurophysiological monitoring to directly assess the integrity of descending spinal motor pathways.

Reduced postactivation depression of soleus H reflex and root evoked potential after transcranial magnetic stimulation.

Postactivation depression of the Hoffmann (H) reflex is associated with a transient period of suppression following activation of the reflex pathway. In soleus, the depression lasts for 100-200 ms during voluntary contraction and up to 10 s at rest. A reflex root evoked potential (REP), elicited after a single pulse of transcutaneous stimulation to the thoracolumbar spine, has been shown to exhibit similar suppression. The present study systematically characterized the effect of transcranial magnetic stimulation (TMS) on postactivation depression using double-pulse H reflexes and REPs. A TMS pulse reduced the period of depression to 10-15 ms for both reflexes. TMS could even produce postactivation facilitation of the H reflex, as the second reflex response was increased to 243 ± 51% of control values at the 75-ms interval. The time course was qualitatively similar for the REP, yet the overall increase was less. While recovery of the H reflex was slower in the relaxed muscle, the profile exhibited a distinct bimodal shape characterized by an early peak at the 25-ms interval, reaching 72 ± 23% of control values, followed by a trough at 50 ms, and then a gradual recovery at intervals > 50 ms. The rapid recovery of two successively depressed H reflexes, ∼ 25 ms apart, was also possible with double-pulse TMS. The effect of the TMS-induced corticospinal excitation on postactivation depression may be explained by a combination of pre- and postsynaptic mechanisms, although further investigation is required to distinguish between them.

Facilitation of descending excitatory and spinal inhibitory networks from training of endurance and precision walking in participants with incomplete spinal cord injury.

After incomplete spinal cord injury (iSCI), training of walking function that emphasizes both endurance and speed may produce different changes in spared neural pathways compared to precision training that emphasizes walking over obstacles and precise placement of the foot. To examine this, 16 participants with iSCI received 2 months of endurance or precision training, in random order, with 2 months of rest before crossing-over to the other type of training. Both forms of training increased the maximum motor-evoked potential (MEPmax) elicited by transcranial magnetic stimulation over the motor cortex, but only in tibialis anterior (TA) muscles that had small (<0.5 mV) MEPmax values before training, no matter when the specific type of training was performed. A similar pattern of training-induced increases in maximum voluntary contractions was also observed. Although walking function was improved by both forms of training, a positive correlation between MEPmax and clinical measures of walking function only occurred after endurance training. Endurance and precision training also increased the excitability of inhibitory spinal networks, as demonstrated by an increase in the suppression of TA MEPs by a prior, low-threshold stimulation to the common peroneal nerve and by increases in the inhibitory component of the cutaneomuscular reflex. The increase in the descending excitation of the spinal cord and the increase in excitability of inhibitory spinal networks may mediate the improved volitional control of walking and reduction of involuntary muscle spasticity, respectively, that are observed in response to intensive motor training in participants with incomplete spinal cord injury.

Post-activation depression in the human soleus muscle using peripheral nerve and transcutaneous spinal stimulation.

Transcutaneous stimulation of the human lumbar spine can be used to elicit root-evoked potentials (REPs). These sensory-motor responses display notable similarities to the monosynaptic H-reflex. The purpose of this study was to compare post-activation depression of the soleus REP to that of the H-reflex, when conditioned by either an H-reflex or an REP. Paired pulses were delivered 25-200ms apart and the recovery was characterized using three levels of stimulation. In all conditions, post-activation depression was reduced during contraction as compared to rest (P<0.001). REP doublets, delivered using an inter-pulse interval of 150ms, recovered to 68±8% of control during plantarflexion and 20±6% of control at rest. During contraction, recovery of a second REP was 65% of the corresponding recovery for a second H-reflex. The recovery of an H-reflex was equivalent, when conditioned by either an H-reflex or an REP, even though the spinal stimulus activated and/or engaged more afferent and efferent fibers. Our results suggest that the additional elements activated by the spinal stimulus did not affect the recovery of the H-reflex. However, the transcutaneous spinal stimulus produced more inhibition when it was assessed using two low-intensity REPs (P<0.05) suggesting that the pathway mediating the spinally-evoked response was more susceptible to being inhibited.

Long-latency, inhibitory spinal pathway to ankle flexors activated by homonymous group 1 afferents.

Inhibitory feedback from sensory pathways is important for controlling movement. Here, we characterize, for the first time, a long-latency, inhibitory spinal pathway to ankle flexors that is activated by low-threshold homonymous afferents. To examine this inhibitory pathway in uninjured, healthy participants, we suppressed motor-evoked potentials (MEPs), produced in the tibialis anterior (TA), by a prior stimulation to the homonymous common peroneal nerve (CPN). The TA MEP was suppressed by a triple-pulse stimulation to the CPN, applied 40, 50, and 60 ms earlier and at intensities of 0.5-0.7 times motor threshold (average suppression of test MEP was 33%). Whereas the triple-pulse stimulation was below M-wave and H-reflex threshold, it produced a long-latency inhibition of background muscle activity, approximately 65-115 ms after the CPN stimulation, a time period that overlapped with the test MEP. However, not all of the MEP suppression could be accounted for by this decrease in background muscle activity. Evoked responses from direct activation of the corticospinal tract, at the level of the brain stem or thoracic spinal cord, were also suppressed by low-threshold CPN stimulation. Our findings suggest that low-threshold muscle and cutaneous afferents from the CPN activate a long-latency, homonymous spinal inhibitory pathway to TA motoneurons. We propose that inhibitory feedback from spinal networks, activated by low-threshold homonymous afferents, helps regulate the activation of flexor motoneurons by the corticospinal tract.

Interaction of transcutaneous spinal stimulation and transcranial magnetic stimulation in human leg muscles.

Transcutaneous spinal stimulation is a noninvasive method that can activate dorsal and/or ventral roots depending on the location and intensity of stimulation. Reflex root-evoked potentials (REPs) were studied in muscles that traditionally evoke large (soleus) and small H-reflexes (tibialis anterior), as well as muscles where H-reflexes are difficult to study (hamstrings). This study characterizes the interaction of the REP and the motor-evoked potential (MEP). Transcranial magnetic stimulation (TMS) delivered 11-25 ms before spinal stimulation resulted in more than linear summation of the two responses. Because of overlap, the modulation was quantified after subtracting the contribution of the conditioning MEP or REP. At rest, the mean-rectified soleus response was facilitated by up to ~250 µV (21-times the MEP or 161% of the REP). The increases were more reliable during a voluntary contraction (up to ~300 µV, 517% of the MEP or 181% of the REP). At the 13-ms interval, the mean-rectified response in the pre-contracted hamstrings was increased by 227% of the MEP or 300% of the REP. In some subjects, TMS could also eliminate the post-activation depression produced using two spinal stimuli, confirming that the interaction can extend to presynaptic spinal neurons. The spatiotemporal facilitation in tibialis anterior was not significant. However, the large MEP was facilitated when the spinal stimulus preceded TMS by 100-150 ms, presumably because of rebound excitation. These strong interactions may be important for inducing motor plasticity and improved training procedures for recovery after neurological damage.

Preservation of motor evoked potentials under anesthesia in children with spinal muscular atrophy type II undergoing spinal deformity surgery.

Spinal muscular atrophy is a progressive condition in which movement is gradually lost as a result of the loss of spinal motor neurons. Individuals with this condition may require surgical correction of a secondary scoliosis. Motor evoked potentials were recorded using transcranial electrical stimulation in four such individuals undergoing surgery. All the patients were nonambulatory and in wheelchairs. Motor evoked potentials were recordable in both upper and lower limb muscles, with similar stimulation parameters to control subjects undergoing surgery for idiopathic scoliosis. The amplitudes of the motor evoked potentials were similar to those in control subjects, although the latencies were shorter reflective of the smaller stature of the spinal muscular atrophy patients. The relative preservation of the motor evoked potentials despite the patients' poor voluntary motor control suggests that there is a selective preservation of the motor neurons mediating the motor evoked potential in spinal muscular atrophy and a maintenance of the conduction velocities of the corticospinal tract.

Facilitation of corticospinal connections in able-bodied people and people with central nervous system disorders using eight interventions.

BACKGROUND: Voluntary contractions (VOL), functional electrical stimulation (FES), and transcranial magnetic stimulation (TMS) can facilitate corticospinal connections. OBJECTIVE: To find the best methods for increasing corticospinal excitability by testing eight combinations: (1) VOL, (2) FES, (3) FES + VOL, (4) TMS, (5) TMS + VOL, (6) paired associative stimulation (PAS) consisting of FES + TMS, (7) PAS + VOL, and (8) double-pulse TMS + VOL. METHODS: Interventions were applied for 3 × 10 minutes in 15 able-bodied subjects, 14 subjects with stable central nervous system lesions (e.g., chronic stroke, and incomplete spinal cord injury) and 16 subjects with progressive central nervous system conditions (e.g., secondary progressive multiple sclerosis). Motor-evoked potentials (MEP), M-waves, and H-reflexes were monitored over a 1-hour period. RESULTS: Three interventions (PAS, PAS + VOL, and double-pulse TMS + VOL) caused 15% to 20% increases (P < 0.05) in the MEP at a stimulus level that initially produced a half-maximal response (MEP(half)) during a contraction. Interventions were less effective in both clinical groups than in the able-bodied group. Interventions with VOL were more effective in increasing the MEP(half) than those without (P = 0.022). When more modalities were combined, the MEP increases were larger (P = 0.022). CONCLUSIONS: (1) Short-term application of FES, TMS, and VOL can facilitate corticospinal pathways, particularly when methods are combined. (2) The effects may depend on the total activation of neural pathways, which is reduced in central nervous system disorders.

Effect of percutaneous stimulation at different spinal levels on the activation of sensory and motor roots.

Percutaneous spinal stimulation is a promising new technique for understanding human spinal reflexes and for evaluating the pathophysiology of motor roots. Previous studies have generally stimulated the T11/T12 or T12/L1 vertebral junctions, sites that overlie the lumbosacral enlargement. The present study sought to determine the best location for targeting sensory and motor roots during sitting. We used paired stimuli, 50 ms apart, to distinguish the contribution of the reflex and motor components which make up the root evoked potential. This assumed that post-stimulation attenuation, primarily through homosynaptic depression, would abolish the second potential if it was trans-synaptic in origin. Conversely, successive responses would be unchanged if motor roots were being stimulated. Here, we show that sensory root reflexes were optimally elicited with percutaneous stimulation over the L1-L3 vertebrae. However, the optimal position varied between subjects and depended on the target muscle being studied. A collision test showed that the reflex recorded in pre-tibial flexors was low in amplitude and was prone to crosstalk from neighbouring muscles. In contrast to the reflex response, direct motor root activation was optimal with stimulation over the more caudal L5-S1 vertebrae. The present results support the utility of paired stimulation for evaluating the topographical recruitment of sensory and motor roots to human leg muscles.

External sensors for detecting the activation and deactivation times of the major muscles used in walking.

Functional electrical stimulation (FES) can improve walking in individuals with mobility impairments. We evaluated accelerometers, force sensitive resistors, segment angles, and segment angular velocities to identify which sensor best determines the activation and deactivation times of the main muscles used during walking. This sensor(s) can be used in the future in conjunction with FES systems to improve walking. Able-bodied subjects walked at various speeds. Threshold levels were set for each sensor that minimized the difference between the times of activating and deactivating the electromyogram (EMG) of six muscles and the times of sensor threshold crossings as a percent of the step cycle. Mobility-impaired subjects walked at their preferred speed with and without FES to correct foot drop. Thresholds were set for these subjects so that sensor signals would cross at times that matched those of able-bodied subjects. Segment angles were generally the most effective sensor signals. Using segment angles of the thigh, shank, and foot, activation and deactivation times of the six muscles could be determined to within 6% of the step cycle. The shank segment angle produced the lowest overall error and was among the top three sensors for 10 of the 12 events (activation and deactivation of six muscle groups). A segment angle sensor was implemented using a complementary filter (accelerometer/gyroscope combination). Using this sensor improved rule-based timing of FES in subjects with foot drop as compared to accelerometers alone.

Volitional muscle strength in the legs predicts changes in walking speed following locomotor training in people with chronic spinal cord injury.

BACKGROUND: It is unclear which individuals with incomplete spinal cord injury best respond to body-weight-supported treadmill training. OBJECTIVE: The purpose of this study was to determine the factors that predict whether a person with motor incomplete spinal cord injury will respond to body-weight-supported treadmill training. DESIGN: This was a prognostic study with a one-group pretest-posttest design. METHODS: Demographic, clinical, and electrophysiological measurements taken prior to training were examined to determine which measures best predicted improvements in walking speed in 19 individuals with chronic (>7 months postinjury), motor-incomplete spinal cord injuries (ASIA Impairment Scale categories C and D, levels C1-L1). RESULTS: Two initial measures correlated significantly with improvements in walking speed: (1) the ability to volitionally contract a muscle, as measured by the lower-extremity manual muscle test (LE MMT) (r=.72), and (2) the peak locomotor electromyographic (EMG) amplitude in the legs (r=.56). None of the demographics (time since injury, age, body mass index) were significantly related to improvements in walking speed, nor was the clinical measure of balance (Berg Balance Scale). Further analysis of LE MMT scores showed 4 key muscle groups were significantly related to improvements in walking speed: knee extensors, knee flexors, ankle plantar flexors, and hip abductors (r=.82). Prediction using the summed MMT scores from those muscles and peak EMG amplitude in a multivariable regression indicated that peak locomotor EMG amplitude did not add significantly to the prediction provided by the LE MMT alone. Change in total LE MMT scores from the beginning to the end of training was not correlated with a change in walking speed over the same period. LIMITATIONS: The sample size was limited, so the results should be considered exploratory. CONCLUSIONS: The results suggest that preserved muscle strength in the legs after incomplete spinal cord injury, as measured by MMT, allows for improvements in walking speed induced by locomotor training.

Short-interval intracortical inhibition with incomplete spinal cord injury.

OBJECTIVE: Short-interval intracortical inhibition (SICI) in leg and hand muscles was characterized in individuals with incomplete spinal cord injury (SCI) to understand how such inhibition limits corticospinal drive after spinal insult. METHODS: We compared SICI during a voluntary contraction in 16 SCI and 14 control subjects, the latter group tested over a larger range of conditioning and test stimulus (CS and TS) intensities to best match the SCI data. RESULTS: The average peak SICI in the tibialis anterior muscle was typically 3-4 times lower in the SCI subjects compared to controls. When matched for absolute TS intensity, in terms of maximum stimulator output, both U-shaped SICI recruitment curves were produced by similar CS intensities. SICI in the first dorsal interosseous muscle of the hand tended to be larger than in the ankle flexor. CONCLUSIONS: Incomplete SCI reduces SICI compared to controls, but the absolute CS intensities that produce the U-shaped SICI recruitment curves are unchanged. SIGNIFICANCE: These findings suggest that although the relative excitability profile of cortical SICI networks is unchanged after SCI, the effective inhibition of corticospinal tract output by these neurons is reduced.

Afferent regulation of leg motor cortex excitability after incomplete spinal cord injury.

An incomplete spinal cord injury (SCI) impairs neural conduction along spared ascending sensory pathways to disrupt the control of residual motor movements. To characterize how SCI affects the activation of the motor cortex by spared ascending sensory pathways, we examined how stimulation of leg afferents facilitates the excitability of the motor cortex in subjects with incomplete SCI. Homo- and heteronymous afferents to the tibialis anterior (TA) representation in the motor cortex were electrically stimulated, and the responses were compared with uninjured controls. In addition, we examined if cortical excitability could be transiently increased by repetitively pairing stimulation of spared ascending sensory pathways with transcranial magnetic stimulation (TMS), an intervention termed paired associative stimulation (PAS). In uninjured subjects, activating the tibial nerve at the ankle 45-50 ms before a TMS pulse in a conditioning-test paradigm facilitated the motor-evoked potential (MEP) in the heteronymous TA muscle by twofold on average. In contrast, prior tibial nerve stimulation did not facilitate the TA MEP in individuals with incomplete SCI (n = 8 SCI subjects), even in subjects with less severe injuries. However, we provide evidence that ascending sensory inputs from the homonymous common peroneal nerve (CPN) can, unlike the heteronymous pathways, facilitate the motor cortex to modulate the TA MEP (n = 16 SCI subjects) but only in subjects with less severe injuries. Finally, by repetitively coupling CPN stimulation with coincident TA motor cortex activation during PAS, we show that 7 of 13 SCI subjects produced appreciable (>20%) facilitation of the MEP following the intervention. The increase in corticospinal tract excitability by PAS was transient (<20 min) and tended to be more prevalent in SCI subjects with stronger functional ascending sensory pathways.

Suppression of EMG activity by subthreshold paired-pulse transcranial magnetic stimulation to the leg motor cortex.

Cortical activity driving a voluntary muscle contraction is inhibited by very low-intensity transcranial magnetic stimulation (TMS) and is reflected in the suppression of the average rectified EMG. This approach offers a method to test the contribution of cortical neurons actively involved in a motor task, but requires a large number of stimuli (approximately 100) to suitably depress the average EMG. Here, we investigated whether two pulses of subthreshold TMS at interstimulus intervals (ISIs) ranging between 1 and 12 ms could enhance the amount of EMG suppression in the tibialis anterior muscle compared to a single pulse. Pairs of subthreshold TMS at an ISI of 7 ms produced the maximum EMG suppression that was 42% more than the inhibition elicited using a single pulse. In addition, the signal-to-noise ratio of the TMS-induced suppression was further increased by a second pulse, delivered 7 ms later. The reduction in the EMG at the 7 ms paired-pulse interval occurred without any short-latency excitation suggesting that the two stimuli increased the activation of cortical inhibitory neurons. Subthreshold paired-pulse TMS at ISIs of 1-3 ms was prone to EMG excitation in the period that immediately preceded the inhibition and is consistent with the recruitment of short-interval intracortical facilitation (SICF). We propose that pairs of subthreshold TMS outside the range of SICF with an inter-pulse interval of 7 ms is optimal to inhibit ongoing cortical activity during human motor movement.

Changes in locomotor muscle activity after treadmill training in subjects with incomplete spinal cord injury.

Intensive treadmill training after incomplete spinal cord injury can improve functional walking abilities. To determine the changes in muscle activation patterns that are associated with improvements in walking, we measured the electromyography (EMG) of leg muscles in 17 individuals with incomplete spinal cord injury during similar walking conditions both before and after training. Specific differences were observed between subjects that eventually gained functional improvements in overground walking (responders), compared with subjects where treadmill training was ineffective (nonresponders). Although both groups developed a more regular and less clonic EMG pattern on the treadmill, it was only the tibialis anterior and hamstring muscles in the responders that displayed increases in EMG activation. Likewise, only the responders demonstrated decreases in burst duration and cocontraction of proximal (hamstrings and quadriceps) muscle activity. Surprisingly, the proximal muscle activity in the responders, unlike nonresponders, was three- to fourfold greater than that in uninjured control subjects walking at similar speeds and level of body weight support, suggesting that the ability to modify muscle activation patterns after injury may predict the ability of subjects to further compensate in response to motor training. In summary, increases in the amount and decreases in the duration of EMG activity of specific muscles are associated with functional recovery of walking skills after treadmill training in subjects that are able to modify muscle activity patterns following incomplete spinal cord injury.